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The design of a fibre Bragg grating based manometry catheter for in-vivo diagnostics in the human colon is presented. The design is based on a device initially developed for use in the oesophagus, but in this instance, longer sensing lengths and increased flexibility were required to facilitate colonoscopic placement of the device and to allow access to the convoluted regions of this complex organ. The catheter design adopted allows the number of sensing regions to be increased to cover extended lengths of the colon whilst maintaining high flexibility and the close axial spacing necessary to accurately record pertinent features of peristalsis. Catheters with 72 sensing regions with an axial spacing of 1 cm have been assembled and used in-vivo to record peristaltic contractions in the human colon over a 24hr period. The close axial spacing of the pressure sensors has, for the first time, identified the complex nature of propagating sequences in both antegrade (towards the anus) and retrograde (away from the anus) directions in the colon. The potential to miss propagating sequences at wider sensor spacings is discussed and the resultant need for close axial spacing of sensors is proposed.
©2009 Optical Society of America
1. Introduction
Constipation, a common cause of morbidity, is estimated to affect between 15 and 27% of the western world [1, 2]. The prevalence increases to 30-40% of people aged > 65 [3]. In the past 20 years there has been a staggering 50-fold increase, from $US29M [4] to $US1.7billion [5], in the costs applied to the diagnostic work-up and subsequent treatment of constipation. Expenditure on laxatives exceeds $US750M and this value is expected to reach > $US850M by 2010 [6]. However, for many patients laxatives do not restore normal bowel habit. Indeed 33% of young females in Australia seeking medical advice for constipation obtain unsatisfactory results from current therapies [7]. Constipation is a heterogeneous disorder and therefore no single therapy or treatment can be sort. If current therapies are to improve we need a more in-depth understanding of the pathophysiologies that underpin the condition. Colonic propagating pressure waves or propagating sequences (PS) are reported to be an important determinant of luminal propulsion and defecation [8–10] and altered colonic PS characteristics may represent important markers of colonic dysfunction [11–13]. However, measurement of human colonic pressure patterns poses substantial methodological challenges and therefore our understanding of both the physiology and pathophysiology of colonic motor patterns remains relatively primitive.
Colonic manometry is one technique used to record colonic PSs [14]. However the current colonic manometric catheters are limited in the data they can gather. These limitations include the number of available recording sites and the overall length of the catheter. This may limit the ability of devices to provide a realistic image of the muscular contractions involved. Therefore while colonic manometry studies have helped to highlight some important pathophysiological data, most attempts to use colonic manometry as a tool to help differentiate constipation subtypes and guide treatment have failed [15, 16]. Improved techniques for recording detailed colonic contractility may help to improve the diagnosis of colon disorders.
In this work we present the design and latest results from a recently developed fibre Bragg grating (fbg) based manometry catheter for colonic diagnostics. The catheter design is based on a device initially developed for oesophageal use [17] in which an array of 10 mm spaced fbg’s positioned along a single optical fibre was used to form a series of pressure sensors along the axis of the catheter. The fbg’s making up the array were spectrally separated which allowed simultaneous interrogation of the whole array of sensors using wavelength division multiplexing (wdm) techniques. In order to upgrade the catheter for use in the colon, a number of changes have been made. Firstly, the human colon is significantly longer than the oesophagus and follows a complex curvature with a series of bends occupying a 3-dimensional region. Therefore, to successfully record manometric data from the entire colon it was necessary to extend the catheter length and number of sensing regions whilst maintaining sensor spacing and overall flexibility. Details of the limitations of existing technologies, the design of our fibre optic catheter to overcome these limitations, and the subsequent human trials using this catheter are presented in the following Sections.
2. Manometry catheter technologies
2.1 Existing technologies
High-resolution manometry (HRM) with 1 cm spacing between recording sites is becoming increasing popular because it enables users to gain a clear picture of normal or abnormal motor patterns [18] and there are two types of manometric catheters currently in common use for colonic pressure recording; solid-state [19, 20] and water-perfused [14, 21]. In addition, two fibre optic techniques have been reported for measurement of intra-luminal pressure, both using Poisson ratio effects due to compression of a compliant outer coating. The first reported technique uses group delay measurements in a chirped fibre Bragg grating [22]; and the second uses spectrally separated grating elements [23]. However, while both are promising candidates for fabrication of very small diameter devices, to the authors’ knowledge at the time of writing, neither of these optical techniques have been rigorously tested in-vivo.
Of the established manometry techniques the maximal number of sensors is limited. For example solid state catheters are restricted to ~36 sensors because the increasing sensor count results in a loss of flexibility as the device has to accommodate increasing numbers of electrical conductors. Restricted by the number of recording sites available, high resolution manometry is generally only used as a diagnostic tool in short regions of the gut such as the oesophagus [18]. Regions such as the colon extend for ~1.2m and propulsive motor patterns in this regions can extend over segments as short as 2cm [24]. Therefore data can either be recorded in high detail over short sections or with increasing loss of information as the spatial resolution between recording sites increases to accommodate the length of the region studied. Examination of short segments of the colon is also problematic since motor patterns are not distributed evenly throughout the colon [13] and therefore data captured in one short segment cannot be extrapolated to infer detail across the whole region. Alternatively, widely spaced sensors can lead to an effect analogous to aliasing in signal processing [25]. In this sense, this process refers to the confusion that results when a signal is sampled at sensor spacing greater than that of the propulsive activity itself.
In practice, using currently available colonic manometry catheters with 7.5 cm [13, 14], and 10 cm [26, 27] sensor spacings, manometric signals may have been measured at spacing more than twice that of many of the propagated events we are trying to record. Therefore current data may have little or no correlation to what is truly occurring.
2.2 Fibre optic catheter design
Using the same spectral detection techniques as for our oesophageal catheter [17] the number of sensors that can be included in a single fibre is limited to approximately 36. This limit is dictated by the need to provide sensors every 1 cm along the catheter which, given requirements for flexibility between substrates and adequate bond lengths only allows a maximum grating length of 3 mm. This short grating length leads to a spectral width (to first zeros) of approximately 1 nm [28]. The distortion of the fibre due to external variations in pressure cause the location of the reflected peak wavelengths to shift as a function of pressure, which, when coupled to the required dynamic range of each sensor determines the minimum wavelength spacing between gratings of approximately 2 nm. This is shown in Figs. 1(a) and 1(b) in which the variation in wavelength of one grating element is shown as the wavelength peak from an adjacent peak varies due to increasing local pressure around that grating element.
Fig. 1 (a) Ingress of the wavelength peak of one channel into that of an adjacent peak as a function of applied pressure; and (b) the cross-talk effect on the static peak due to the ingress of the varying peak. The dynamic range of the sensor array is determined by the point at which the proximity of one peak starts to affect the measured wavelength of the adjacent peak.
The dynamic range of the sensor array is therefore defined by the point at which the wavelength peak from one sensor starts to impact on the peak of an adjacent sensor. In the example given the sensors had a pressure sensitivity of ~0.001 nm/mmHg which provides greater than 1200 mm/Hg dynamic range. This is more than enough to record even the most extreme of pressures generated within the human digestive tract. The sensor count is then determined by the number of 2 nm wide spectral slices that can be positioned within the available optical bandwidth of the light source and detector. The unperturbed spectrum from one fibre array is shown in Fig. 2 . The grating elements are approximately 3 dB in reflection and are produced by FBGS (http://www.fbgs-technologies.com) using a draw tower writing technique in high numerical aperture (NA) single mode fibre [29]. The draw tower technique has been a significant enabling technology for these devices as it allows gratings to be written without loss in mechanical strength of the fibre, hence providing an acceptable overall robustness of the sensor array. In order to extend the range of the sensing region, a second fibre has been used with a second array of spectrally separated gratings covering nominally the same wavelength region and then switching between the fibres to increase the overall achievable sensor count. The fibres are positioned so that the grating arrays lie in series thus extending the overall length of the sensing region. To form the catheter the sensing array is covered with an outer bio-compatible elastomeric sleeve; further details of the catheter construction are given in Reference 17. The full data acquisition is then achieved by switching between the fibres at a fast enough rate to maintain an acceptable data acquisition frequency (typically 10 Hz is adequate for colonic manometry). Optical switching at this rate is readily achievable and the spectral detector used for this work had this feature built in (custom fbg interrogator unit supplied by FOS&S, http://www.fos-s.be).
Fig. 2 Reflection spectrum recorded from a single fibre containing a 36 element Draw Tower Grating array. Note that the variation in peak amplitudes is due to the gain variation of the detector not to variation in grating strength.
Using multiple fibres in this way can adversely affect the flexibility of the catheter due to the very limited axial elasticity of the fibre; for example, having two fibres following separate linear paths through the catheter would prevent the catheter flexing in the plane defined by the fibre pair. To counter this problem the fibres are woven into the substrates so that they cross over on the axis of the catheter between each sensing region, as shown in Fig. 3 . Care was needed to weave the fibre without creating small bend radii between the substrates leading to progressive loss of the optical signal down the length of the catheter. This was addressed by using the high NA fibre (NA > 0.2) that can tolerate bend radii of ~5 mm without loss and a catheter design (1 cm pitch with a sensor diameter of 2.2 mm) that resulted in curves with minimum radii of ~1.5 cm so this problem is successfully avoided. The woven aspect of the catheter has allowed us to maintain the high level of flexibility needed to access the convoluted regions of the human colon while doubling the length of the 1 cm spaced sensing region.
Fig. 3 Fibre optic sensor array woven into substrates. Note the cross over of the fibres to facilitate flexibility of the catheter
Using the design outlined above we have fabricated a 72 element device and have recorded HRM data over a physiologically significant length of the human colon for the first time. To our knowledge, our fibre optic catheters currently represent the only technology that can achieve the required number and spatial density of sensing regions to allow us to record HRM data over extended regions of the human colon.
3. Colonic recording and data analysis
3.1 Catheter placement and measurement protocols
Prior to the fibre-optic catheter placement, the colon was prepared (washed out) by oral administration of two litres of a polyethylene glycol (Golytely; Braintree Laboratories, Braintree, Massachusetts, USA). The distal tip of the catheter was clipped to the mucosal wall of the colon using two hemoclips (Olympus America, Melville, NY) to prevent the catheter from moving during subsequent data acquisition. Placement of colonic catheters has been described in detail previously [30]. The 72 element fibre optic catheter has been placed colonoscopically into two female patients with severe slow transit constipation (both participants had given written, informed consent and the studies were approved of in Australia by the Human Ethics Committees of the South Eastern Area Health Service, Sydney and the University of New South Wales). X-ray images showing the location of the catheters are shown in Fig. 4 . In the first instance (patient ‘EW’; 34yrs) the catheter tip was clipped to the mucosa of the mid-Ascending colon. Sensors 1-10 are located in the ascending colon; 12-32 in the transverse colon; 35-61 in the descending colon; 63-72 in the sigmoid colon. In the second patient (‘IP’; 62 yrs) the catheter tip is clipped to the distal transverse colon. In this patient sensors 1-10 are located in the transverse colon; 11-36 in the descending colon and 37-72 in sigmoid colon/rectum. After recovery from sedation, all subjects were transferred to a private room where they slept overnight. A standard meal was given at 18:00. Recording commenced at 08:00 (day 2), approximately 22 hours after intubation, to allow for washout of drugs. Recording was then continued for 24 hours.
Fig. 4 Location of the fibre optic catheter in two female patients with slow transit constipation. A. ‘EW’, 34yrs & B ‘IP’ 62yrs
3.2 Data analysis procedure
After the trial was complete the data was analyzed to identify propagating sequences (PS) along the colon. These motor patterns are a major determinant of propulsion in the colon [9] and the definition of PS’s has been described in detail previously [10, 13]. Briefly, a PS is defined as a sequence of 3 or more pressure waves recorded from adjacent recording sites in which the conduction velocity within that sequence lay between 1 and 12 cm/sec. Propagating sequences were further qualified by the terms antegrade (towards the anus) or retrograde (away from the anus), depending upon the direction of propagation.
The data was initially analysed using the full data set from the 1 cm spaced sensors in order to correctly identify all PS’s and define a standard for subsequent data analyses. The data set was then re-analysed using sub-sets of the data from recording sites spaced at 7 cm and 10 cm to simulate recordings from currently used colonic catheters [10, 13, 26, 27].
Spatiotemporal maps of PS activity recorded from patient EW has been displayed in Fig. 5 . Within this map each individual ridge represents a PS. Antegrade PSs (green) originate at the orad end of the ridge and retrograde PSs (red) originate at the anal end of the retrograde ridge. The start of each antegrade and retrograde ridge indicates the site of origin within the colon that the PS started and the time of day the PS occurred. The length of the ridge indicates the extent of propagation, and the shading within and height of the ridge indicates the amplitude of the component pressure waves. The light-blue hatched lines represent the location of the mid-colon (splenic flexure). This graphical form provides an easy to interpret comparison between each of the sub-sample data sets and the 1 cm spaced (top); 7 cm spaced (middle) and 10 cm spaced (bottom). The implications of the data will be discussed further in Section 4.
Fig. 5 Twenty four hour spatiotemporal maps of antegrade and retrograde propagating sequences recorded in patient EW. The maps indicate comparisons of the number of detected PSs between (A) 1cm spacing, (B) 7cm spacing and (C) 10cm spacing. The details of each image are given in the text.
4. Discussion
4.1 Variations between the standard and sub-sampled data sets
The spatiotemporal maps displayed in Fig. 5 and in Table 1 clearly demonstrate the number of PSs that are potentially missed when the sensor spacing is too great. At 1 cm spacing, detection of both antegrade and retrograde PSs is dramatically increased compared to those identified at 7 and 10 cm spacing, and closer examination of the 1 cm data shows a wealth of short-extent PSs, particularly in the retrograde direction that is simply missed in the more widely spaced data. Clearly, using catheters with widely spaced sensors does not allow the true nature of the complex nature of colonic peristalsis to be resolved, and even slight variation in the location of the catheter sensors within the colon can have an effect upon the number of PSs detected, resulting in significant ramifications on the analysis of colonic function.
Table 1. Antegrade and retrograde PS frequency at each of the different special settings.
4.2 Analysis of localized periods of activity
To indicate how the PSs were being misrepresented by the sub-sampled data sets, we now show detailed analyses of a short period of activity. Figure 6 shows an example of a short section of a manometry trace recorded from patient IP. The middle image (B) shows data recorded from every 10th sensor. In this instance only a single antegrade PS has been identified (red arrow). However, in the full data set (C) an array of short range retrograde PSs (blue arrows) are clearly identified. This misrepresentation can be likened to sub-sampling in data processing when the sample rate is less than the Nyquist limit [25]. It is clear from this example that using widely spaced sensors is inadequate for accurately identifying the complex nature of the PSs present in the human colon.
Fig. 6 An X-ray image showing placement of the catheter in patient IP (A); and manometric traces of colonic motor patterns recorded from the distal-transverse to the rectum. The manometric trace in the middle (B) shows that data recorded at 10 cm intervals. The manometric trace on the right (C) shows the data from the full array of recording sites. Further details are given in the text.
5. Conclusion
Through the use of a recently developed fibre optic HRM catheter we have recorded and analysed the complex motor patterns that contribute to peristalsis over an extended region of the human colon. This is the first time that HRM data has been recorded from such an extended region in the colon and the results have demonstrated the potential problems that may be associated with using data from widely spaced manometry catheters for identifying biomarkers for health and diseased states. This work further suggests that it will be necessary for pan-colonic HRM recordings to become an accepted gold standard for diagnostics before any realistic and reliable biomarkers can be set for colonic motility. We believe that this technology will provide a potentially revolutionary means for diagnosing colonic motility disorders.
Acknowledgements
Drs Dinning and Szczesniak are supported by NHMRC Australia. Mr Wiklendt is supported by a St. George Medical Research Foundation seed grant.
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